PETER GOODWIN: Younger women with early breast cancer treated with mastectomy had lower mortality at 20 years than those receiving breast-conserving therapy—in another study reported to the ESTRO meeting in Turin. First author Tinne Laurberg from Denmark made the discovery by long-term follow up of large groups of women with low-risk disease.

IN: “We wanted to see how the long-term effect was among low-risk patients, especially among the young ones. Because we know that this, especially this group, have a higher local recurrence rate. And we wanted to see if this local recurrence rate possibly translated into a higher mortality.”

PETER:

Young women need to know whether they would be better off with mastectomy, or whether breast-conserving therapy is indeed okay for them.

TINNE LAURBERG:

“Yeah. We wanted to look at the long-term follow-up and see, yeah, what the difference between breast-conserving therapy and mastectomy in the group of very young women with low-risk breast cancer.”

PETER:

What did you do in the study?

TINNE LAURBERG:

“In the study years period from 1989 to 98, we collected all data from all Danish breast cancer patients below 40 years, from [natural liffe]. And then when we had the older ones from a part of Denmark, because it was important for us to get a balanced proportion of patients with, young of age. Because they will not only represent a small fraction of all breast cancer patients. So it was important for us that we have all the young ones included.”

PETER:

So you defined young as?

TINNE LAURBERG:

“We ended up defining young as 45 years old, but that was actually based on the data.”

PETER:

And what did you find when you looked at breast-conserving therapy and the patterns of local recurrence, and indeed distant metastases?

TINNE LAURBERG:

“Yeah. We find a very distinct pattern. Among the patients below 45 years, they had a higher local recurrence rate, compared to the older ones. And more interesting, they have a 2.7 higher risk of getting distant metastases than the ones having mastectomy.”

PETER:

What about the women over 45, in terms of local recurrence?

TINNE LAURBERG:

“In general the local recurrence rate was low. And it was very interesting to see that none of them had, if they have a local recurrence, no none of them had a distant metastasis later or simultaneously. So it would, so based on our data it would be safe to offer a woman, low-risk woman, older than 45 years, a breast-conserving therapy.”

PETER:

Right. So local recurrence is one thing.

TINNE LAURBERG:

“Yeah!”

PETER:

But of course ultimately distant metastases and overall mortality is the big thing.

TINNE LAURBERG:

“Yeah, yes!”

PETER:

So it seems it’s okay for older women.

TINNE LAURBERG:

“Yeah, yeah, all that defined as 45 years. So actually that’s the point. So normally you won’t think that a person 46 is an older woman. So it’s very important to have it in this context.”

PETER:

Right. Now for the women younger than 45 years of age, they’re low-risk but they had a small tumor and are lymph node-negative. What did you find, in fact, in terms of what could be the change of recommendations?

TINNE LAURBERG:

“Actually, I do not like to say change of recommendations, because it’s, you have to be aware that these women have no adjuvant systemic treatment. And today all of them would have adjuvant systemic treatment. And because of that I will expect that the local recurrence rate would be lower in the breast-conserving therapy group of younger patients. So I can only say that if they have not had adjuvant systemic treatment, then they have a higher risk of distal metastases, and all-cause mortality among the young patients having breast-conserving therapy, compared to compared to mastectomy.

Durn: 3:58secs

PETER:

That was Tinne Laurberg, from the Department of Experimental Clinical Oncology at Aarhus University Hospital, in Denmark. In the group of patients treated with mastectomy all local recurrence occurred within the first ten years. But in contrast, patients who had breast-conserving therapy had local recurrences beyond ten years and had a significantly higher cumulative incidence of recurrences by 20 years’ follow up. In the young patients local recurrence was associated with distant metastasis, and breast-conserving therapy was associated with a significantly higher mortality! Whereas: among older patients local recurrence was not a prognostic marker for distant metastases and there was no difference in breast cancer mortality between the two treatment groups. Hmmm.

PETER:

And I asked Sofia Riviera, from Paris, to comment on these new data that have perhaps made the clinical decision-making about whether to go for mastectomy or breast-conserving therapy a bit harder to make:

IN: “In fact the results of the study presented by Tinne, which is a Danish randomized trial, show that in younger patients, below 45 years, it might make a difference to have a mastectomy versus breast-conserving surgery plus radiotherapy. In fact, older data have shown that there was no difference in survival. And in this study what we can see is that, specifically for these younger patients, we have a difference where mastectomy was, where the trial was in favor of mastectomy versus breast-conserving surgery plus radiotherapy.”

PETER:

Now this was a study with a large number of patients younger than 45 years of age. And continued for a long time. Is it because you now have enough data on young women that you can actually say that, potentially, mastectomy could be more protective?

SOFIA RIVIERA:

“Well we have to be very cautious because yes, it’s a large number of patients, it’s a long overall survival and a long follow-up with more than 17 years of follow-up. But in this trial there was no systemic treatment. And nowadays some of these patients might have systemic treatment. So that might be a confounding factor that we have to take into account.”

PETER:

Right. So in this historical data, because systemic treatment wasn’t going to happen in patients with low-risk disease, the data as it were clean and there is a fairly clean result. How big a difference do you think adjuvant systemic treatment can make?

SOFIA RIVIERA:

“Well for these very, for these low-risk patients, I think we have to distinguish the very low-risk patients where we might not need any systemic treatment, only hormonal treatment. And the low-risk patients with a little bit higher risk inside the low group. And these patients might still need systemic treatment. So that’s where the difference will be, and that’s probably something that will help us to build other trials in order to validate the strategy that we should adapt in choosing mastectomy versus breast-conserving surgery for these young patients.”

PETER:

Okay, now a patient comes in to your office tomorrow. She has a tumor that’s less than five centimeters, and node-negative. What’s your advice to her right now, do you think?

SOFIA RIVIERA:

“Well it really depends on the characteristic of her tumor and on one of the stages, HER2 stages. And this wasn’t really fully evaluated in the trial presented by Tinne because she had a very small number of patients HER2 over-expressed. So typically for that kind of patient I will look into the genetic profile, and probably propose a test with a signature to orientate my strategy in choosing whether I will do or not the systemic treatment.”

PETER:

And what about mastectomy? Do you think there will be a resurgence of more interest in mastectomy for young women with low-risk disease?

SOFIA RIVIERA:

Well I’m not completely sure about it. Mastectomy still is something very invasive, especially for young women. And so before concluding that, and saying that would be worthy to do the mastectomy to avoid systemic treatment, I will be very cautious. And confirm that with a trial in which systemic treatment is evaluated.”

PETER:

So how would you sum this up in a few words then, where we stand, and what the recommendations could become?

SOFIA RIVIERA:

“I think this trial doesn’t change the recommendation nowadays. It just raises some new questions, brings some new data that point out the fact that in this specific sub-group of patients that are younger than 45 years, we should reconsider the options and we should design specific trials for that.”

Durn: 3:50”

PETER:

Sofia Riviera, Head of the Breast Cancer Unit in the Department of Radiation Therapy at the Institut Gustave Roussy, in Paris.